In vitro modelling of bone infection for osteomyelitis and osteoradionecrosis

Bone infections, including osteomyelitis and osteoradionecrosis, cause significant morbidity and mortality, especially in elderly people where osteomyelitis is the second most critical musculoskeletal infection. These conditions can have devastating consequences, including severe pain, bone destruction, amputation, and even sepsis and death. Current treatments often have limited success, and the development of more effective therapies requires a better understanding of the underlying mechanisms of disease development/aetiology. There is a critical need for models that accurately replicate the pathophysiology of bone infections.

The use of animal models for studying bone infections has provided valuable insights into the pathophysiology of these diseases. However, animal models have several limitations, including ethical concerns, high cost, and poor reproducibility. In vitro models that accurately replicate the pathophysiology of these infections could offer an alternative to animal testing, allowing researchers to explore the complex interactions between microbial pathogens, immune endothelial cells, and bone-resident osteoblasts/osteocytes in a more controlled and reproducible manner.

In vitro models could facilitate the exploration of complex interactions between microbial pathogens, endothelial cells, and bone-resident cells, leading to a better understanding of these diseases and the development of more effective treatments. Despite the recent advances tissue engineered organotypic in vitro models of bone, there are still a critical lack of models mimicking the pathophysiology of infected bone, such as osteomyelitis or infection, associated with the development of necrotic tissue due to radiation – collectively known as osteoradionecrosis.

Here, we propose develop advanced in vitro models of osteomyelitis and osteoradionecrosis, with the ultimate goal of replacing animal models that cause severe harm. We will advance 3D iPSCs-based cell cultures, 3D-fluidic chips platforms, and hybrid hydrogels to overcome these challenges and construct vascularised in vitro models of bone. Furthermore, we will irradiate and infect the cultures to generate models of osteoradionecrosis.